Diffuse Alveolar Hemorrhage (DAH)

Epidemiology

  • Prevalence of Etiologies (From Retrospective Review of 34 Cases; Am J Surg Pathol, 1990) [MEDLINE]
    • Systemic Vasculitis (Most Commonly Wegener’s Granulomatosis): 41% of cases
    • Pulmonary-Renal Syndrome: 14% of cases
    • Goodpasture’s Syndrome (see Goodpasture’s Syndrome, [[Goodpastures Syndrome]]): 12% of cases
    • Idiopathic Pulmonary Hemosiderosis (see Idiopathic Pulmonary Hemosiderosis, [[Idiopathic Pulmonary Hemosiderosis]]): 12% of cases
    • Connective Tissue Disease: 12% of cases
    • Other: 9% of cases

Etiology

Vasculitis/Immunologic (see Vasculitis, [[Vasculitis]])

Lung Transplant Rejection/Dysfunction (see Lung Transplant Rejection/Dysfunction, [[Lung Transplant Rejection]])

Coagulopathy

  • General Comments: usually results in diffuse alveolar hemorrhage in association with an underlying pulmonary disease, such as lung cancer/bronchiectasis/infection, or with combination of anticoagulants
  • Acquired Vitamin K Deficiency (see Vitamin K, [[Vitamin K]])
  • Anticoagulation
    • Coumadin (see Coumadin, [[Coumadin]])
    • Factor IIa (Thrombin) Inhibitors (see Factor IIa Inhibitors, [[Factor IIa Inhibitors]])
      • Argatroban (Acova) (see Argatroban, [[Argatroban]])
      • Bivalirudin (Angiomax, Angiox) (see Bivalirudin, [[Bivalirudin]])
      • Dabigatran (Pradaxa) (see Dabigatran, [[Dabigatran]])
      • Desirudin (Iprivask, Revasc) (see Desirudin, [[Desirudin]])
      • Lepirudin (Refludan (see Lepirudin, [[Lepirudin]])
    • Factor Xa Inhibitors (see Factor Xa Inhibitors, [[Factor Xa Inhibitors]])
      • Apixaban (Eliquis) (see Apixaban, [[Apixaban]])
      • Betrixaban
      • Danaparoid (Orgaran) (see Danaparoid, [[Danaparoid]])
      • Edoxaban (Lixiana) (see Edoxaban, [[Edoxaban]])
      • Fondaparinux (Arixtra (see Fondaparinux, [[Fondaparinux]])
      • Rivaroxaban (Xarelto) (see Rivaroxaban, [[Rivaroxaban]])
    • Heparins
      • Dalteparin (Fragmin) (see Dalteparin, [[Dalteparin]])
      • Enoxaparin (Lovenox) (see Enoxaparin, [[Enoxaparin]])
      • Heparin (Unfractionated) (see Heparin, [[Heparin]])
  • Antiphospholipid Antibody Syndrome (see Anti-Phospholipid Antibody Syndrome, [[Anti-Phospholipid Antibody Syndrome]])
  • Antiplatelet Agents
  • Disseminated Intravascular Coagulation (DIC) (see Disseminated Intravascular Coagulation, [[Disseminated Intravascular Coagulation]])
  • IIb/IIIa Inhibitors (see IIb IIIa Inhibitors, [[IIb IIIa Inhibitors]])
    • Abciximab (ReoPro) (see Abciximab, [[Abciximab]])
    • Eptifibatide (Integrilin) (see Eptifibatide, [[Eptifibatide]])
    • Tirofiban (Aggrastat) (see Tirofiban, [[Tirofiban]])
  • Thrombocytopenia (see Thrombocytopenia, [[Thrombocytopenia]])
    • Acute Leukemia Post-Chemotherapy Induction (high-risk of thrombocytopenia-associated diffuse alveolar hemorrhage): these patients may also have evidence of diffuse alveolar damage, infection, or oxygen toxicity on autopsy
    • Immune Thrombocytopenic Purpura (ITP) (see Immune Thrombocytopenic Purpura, [[Immune Thrombocytopenic Purpura]])
    • Acquired Thrombotic Thrombocytopenic Purpura (TTP) (see Thrombotic Thrombocytopenic Purpura-Acquired, [[Thrombotic Thrombocytopenic Purpura-Acquired]])
  • Thrombolytics (see Thrombolytics, [[Thrombolytics]])

Drug

Other

Diffuse Alveolar Damage (DAD)/Acute Respiratory Distress Syndrome (ARDS)

  • See Acute Respiratory Distress Syndrome, [[Acute Respiratory Distress Syndrome]])
  • Diffuse Alveolar Damage is the Most Common Pathologic Finding in ARDS
  • Etiologies of Diffuse Alveolar Damage (DAD)
    • Acute Interstitial Pneumonia (AIP)
    • Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome, [[Acute Respiratory Distress Syndrome]])
      • Aspiration Pneumonia (see xxxx, [[xxxx]])
      • Drugs: cytotoxic agents, chemotherapy, antibiotics
      • Massive Transfusion
      • Pneumonia: viral, bacterial, Pneumocystis Jirovecii
      • Sepsis (see xxxx, [[xxxx]])
      • Trauma
    • Connective Tissue Disease
    • Idiopathic Pulmonary Fibrosis (IPF) (see Idiopathic Pulmonary Fibrosis, [[Idiopathic Pulmonary Fibrosis]])
    • Radiation Therapy/Radiation Pneumonitis (see Radiation Therapy, [[Radiation Therapy]] and Radiation Pneumonitis and Fibrosis, [[Radiation Pneumonitis and Fibrosis]])
    • Toxic Inhalation

Diagnosis

Complete Blood Count (CBC) (see Complete Blood Count, [[Complete Blood Count]])

Serum Chemistry

  • Elevated Creatinine: may be seen in cases with renal involvement

Arterial Blood Gas (ABG) (see Arterial Blood Gas, [[Arterial Blood Gas]])

Chest X-Ray (see Chest X-Ray, [[Chest X-Ray]])

  • xxx

Chest CT (see Chest Computed Tomography, [[Chest Computed Tomography]])

  • Findings
    • Alveolar Filling/Consolidation
    • Ground Glass Infiltrates
    • Interstitial Fibrosis: seen in chronic/Recurrent cases
  • Example: diffuse alveolar hemorrhage in a patient with Wegener’s granulomatosis -> note the ground glass infiltrates in the right lung and extensive alveolar filling in the left lung (alveolar hemorrhage was confirmed in the left lower lobe by bronchoscopy)

WEG DAH

Pulmonary Function Tests (PFT’s) (see Pulmonary Function Tests, [[Pulmonary Function Tests]])

  • Restriction
  • DLCO
    • Increased During Acute Diffuse Alveolar Hemorrhage: resolves within 48-72 hrs (as hemoglobin is degraded to hemosiderin)

Anti-Neutrophil Cytoplasmic Antibody (ANCA) (see Anti-Neutrophil Cytoplasmic Antibody, [[Anti-Neutrophil Cytoplasmic Antibody]])

  • p-ANCA: much less specific than c-ANCA titers
    • p-ANCA: can be positive in microscopic polyangiitis, Churg-Strauss, pauci-immune glomerulonephritis, some cases of isolated pulm capillaritis, polyarteritis nodosa, and ulcerative colitis

Bronchoscopy (see Bronchoscopy, [[Bronchoscopy]])

  • Bronchoalveolar Lavage (BAL): necessary to rule out infection and other etiologies of alveolar infiltrates
    • Increasingly Serial Bloody BAL Fluid is Diagnostic
    • Cell Count and Differential:: presence of hemosiderin-laden macrophages suggests chronic hemorrhage (rather than biopsy-related bleeding)
      • Quantitative Scoring of Alveolar Macrophage Hemosiderin Concentration: sensitive for diagnosis of DAH

Video-Assisted Thoracoscopic Surgery (VATS) with Lung Biopsy (see Video-Assisted Thoracoscopic Surgery, [[Video-Assisted Thoracoscopic Surgery]] and Open Lung Biopsy, [[Open Lung Biopsy]])

  • May Be Used in Cases with Equivocal Serology: but is usually not necessary

Renal Biopsy (see Renal Biopsy, [[Renal Biopsy]])

  • May Be Positive: even in the absence of overt renal involvement

Clinical Manifestations

Pulmonary Manifestations

  • Duration of Symptoms: symptoms usually present for days-weeks

Acute Respiratory Failure (see Respiratory Failure, [[Respiratory Failure]])

  • Epidemiology: may occur in severe cases

Alveoar Infiltrates/Pneumonia-Like Presentation

  • Clinical
    • Cough
    • Chest Pain
    • Dyspnea
    • Fever

Diffuse Pulmonary Ossification (DPO) (see Diffuse Pulmonary Ossification, [[Diffuse Pulmonary Ossification]])

  • Epidemiology: diffuse alveolar hemorrhage has been reported to precede DPO in some cases

Hemoptysis (see Hemoptysis, [[Hemoptysis]])

  • Epidemiology: xxx

Interstitial Pulmonary Fibrosis (see Interstitial Lung Disease, [[Interstitial Lung Disease]])

  • Epidemiology: occurs with recurrent diffuse alveolar hemorrhage

Treatment

  • Post-BMT Diffuse Alveolar Hemorrhage: steroids (solumedrol 125-250 mg q6 hrs x 4-6 days, then taper over 2 wks) improve resp status and survival

References

  • A clinicopathologic study of 34 cases of diffuse pulmonary hemorrhage with lung biopsy confirmation. Am J Surg Pathol 1990; 14: 1112-1125 [MEDLINE]
  • Isolated pulmonary capillaritis and diffuse alveolar hemorrhage in rheumatoid arthritis and mixed connective tissue disease. Chest. 1998 Jun;113(6):1609-15 [MEDLINE]
  • Antiphospholipid antibodies as a cause of pulmonary capillaritis and diffuse alveolar hemorrhage: a case series and literature review. Semin Arthritis Rheum. 2005 Dec;35(3):154-65 [MEDLINE]